Quiescence regulator Foxp1 restrains antigen-induced T cell activation and response by mechanisms including a novel negative feedback loop (121.17)

Abstract Previously we have shown that transcription factor Foxp1 is an essential regulator in maintaining the quiescence of naive T cells during homeostasis. In mice, Foxp1 has four isoforms. Now we find that whereas the full-length Foxp1A is constitutively expressed in mature T cells, T cell receptor (TCR) stimulation induces the expression of a short Foxp1 isoform, Foxp1D, which in turn dampens TCR signaling and T cell proliferation, constituting a negative feedback loop. In Foxp1D conditional transgenic mice, Foxp1D transgene in T cells reduces the generation of CD8+ and CD4+ T effectors to viral infections. On the contrary, Foxp1-deficient T cells (lacking all Foxp1 isoforms) elicit a faster and stronger effector response to antigen challenge. These results suggest that quiescence gene Foxp1 plays an important role in restraining antigen-induced T cell activation and response with a novel negative feedback loop by Foxp1D.